Medical devices such as catheters, guide wires, retractable sheaths and stents commonly have surface coatings that are intended to increase the physical performance of the device and enhance longevity. Of particular interest are hydrophilic coatings which may also impart lubricity to the coated device.
Lubricity describes the property of “slipperiness” or “smoothness”. Lubricious coatings are particularly useful for intracorporeal devices where their lubricity results in reduced frictional forces once a device is introduced and moved within the body, thereby enhancing patient comfort and reducing inflammation and tissue trauma. Lubricious coatings vary in composition but for use in an aqueous environment in vivo, such coatings are typically hydrophilic and wettable. As well as reducing friction, hydrophilic coatings also tend to be resistant to protein adhesion, therefore they have the potential to reduce or eliminate thrombosis. Examples of hydrophilic coating materials include coatings based on polyvinylpyrrolidone, poly(ethylene oxide) and polyurethane, as described in U.S. Pat. No. 4,642,267 and U.S. Pat. No. 6,461,311.
The manufacture of hydrophilic, lubricious coatings for use in vivo can present various difficulties. Such coatings are often prepared using organic solvents where residual traces of which must be removed to be below toxic limits according to current guidance and practice. Coated medical devices must also be able to withstand sterilisation procedures without the coating being chemically and/or physically altered or delaminated from the device.
One approach to forming a hydrophilic coating is to physically entrap functional hydrophilic polymers within a network of a supporting polymer that provides the necessary adherence to the surface of a substrate. These coatings are often referred to as interpenetrating networks (IPNs) and generally consist of a first functional polymer that imparts the desired properties to the coating (in this case hydrophilicity) and a supporting polymer that is chemically cross-linked in order to form a cross-linked polymer network. WO2008/130604 discloses an IPN formed by interspersing a hydrophilic polymer network such as polyethylene glycol with ionisable monomers such as acrylic acid, then polymerising the ionisable monomer to form the IPN, which when swollen with water is said to form coatings of high compressive strength and lubricity.
However, a disadvantage of having the hydrophilic polymer entrapped within an IPN rather than being chemically bonded to the coating is that the hydrophilic polymer may migrate out of the IPN over time. As such, the coating will gradually lose hydrophilicity. More significantly, however, the release of such particulates from the coatings of intracorporeal devices may pose a health risk for patients. Therefore, minimizing particulation is of importance for many medical devices. It should be noted that particulation is not just a concern for IPNs—all polymer coatings can potentially form particulates on the surface which can be released in vivo.
While the release in vivo of particulates/aggregates (known as particulation) from the surface of a coating may pose difficulties in the design and manufacture of the coating, removal of the coating itself via delamination or detachment from the substrate is also potentially a problem, both in terms of the health risks mentioned above and of the durability of the coating.
Considering durability, a coating can be removed from a substrate either by gradual erosion of the substance of the coating and/or by the coating being detached from surface of the substrate. Thus, one way to enhance the durability of a coating is to strengthen the binding between the coating and the surface of the substrate. This can be achieved, inter alia, by treating the surface to be coated with a primer in order to achieve better adhesion between the coating and the surface.
An ideal primer is one that can be universally applied to any substrate. In this regard, the use of polydopamine as a primer has attracted great interest since the discovery that simple immersion of a substrate in a dilute aqueous solution of dopamine, buffered to alkaline pH, results in the spontaneous deposition of a polydopamine film on the substrate. Messersmith et al. (Science, 2007, 318, 426-430) demonstrated that a polydopamine coating is able to form on virtually any type of substrate surface, including metals, metal oxides, ceramics, synthetic polymers and a wide range of other hydrophilic and hydrophobic materials. Polydopamine coatings have been used as a platform for the conjugation of synthetic polymers or biomolecules to a surface, as illustrated in WO2011/005258 which discloses the attachment of amine-functionalised polyethylene glycol (“PEG-NH2”) to a polydopamine coating, to provide a hydrophilic outer layer for the prevention of biofilm formation.
Coatings which are hydrophilic and preferably lubricious can be advantageously modified to include an agent having pharmacological activity, such as an anticoagulant, to impart further beneficial properties to the coating. US 2003/0135195 teaches a medical device such as a catheter with a highly lubricious hydrophilic coating formed from a mixture of colloidal aliphatic polyurethane polymer, an aqueous dilution of poly(1-vinylpyrrolidone-co-2-dimethylaminoethylmethacrylate)-PVP and dendrimers. The document teaches that the coating can be applied to the device by dipping the device in a colloidal dispersion of the aliphatic polyurethane polymer in a solution of poly(1-vinylpyrrolidone-co-2-dimethylaminoethylmethacrylate)-PVP and an active agent (e.g. heparin) in a mixture of dendrimer, water, N-methyl-2-pyrrolidone and triethylamine. The document also teaches that heparin can be contained in the voids within the dendrimers, and that the loaded heparin will elute from the hydrophilic polymer matrix at a predetermined rate.
In summary, there remains a need for improved hydrophilic coatings for surfaces, particularly for the surfaces of devices that are inserted into the body. Preferably, such coatings are lubricious, durable, non-toxic, low particulating, sterilizable, biocompatible and readily applied to a surface.